PTLD may spontaneously regress on reduction or cessation of immunosuppressant medication, and can also be treated with addition of anti-viral therapy. In some cases it will progress to non-Hodgkin's lymphoma and may be fatal. A phase 2 study of adoptively transferred EBV-specific T cells demonstrated high efficacy with minimal toxicity.

Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.

Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.

Second line therapies include: mycophenolate mofetil (cellcept) which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement.

Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (>90%) With this treatment most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%) and have elimination of peripheral blood DNTs. Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin and it has not been reported to cause hypogammaglobulinemia. Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires therapeutic drug monitoring. It is the second most commonly used agent in patients that require chronic therapy. It is mostly well tolerated (though side effects include mucositis, diarrhea, hyperlipidemia, delayed wound healing) with drug-drug interactions. It has better activity against autoimmune disease and lymphoproliferation than mycophenolate mofetil and other drugs; however, sirolimus requires therapeutic drug monitoring and can cause mucositis. A risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence. Its mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. The Goal serum trough is 5-15 ng/ml and can consider PCP prophylaxis but usually not needed.

Other treatments may include drugs like Fansidar, mercaptopurine: More commonly used in Europe. Another is rituximab but this can cause lifelong hypogammaglobulinemia and a splenectomy but there is a >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis

AML-M5 is treated with intensive chemotherapy (such as anthracyclines) or with bone marrow transplantation.

Natural killer (NK) cell therapy is used in pediatrics for children with relapsed lymphoid leukemia. These patients normally have a resistance to chemotherapy, therefore, in order to continue on, must receive some kind of therapy. In some cases, NK cell therapy is a choice.

NK cells are known for their ability to eradicate tumor cells without any prior sensitization to them. One problem when using NK cells in order to fight off lymphoid leukemia is the fact that it is hard to amount enough of them to be effective. One can receive donations of NK cells from parents or relatives through bone marrow transplants. There are also the issues of cost, purity and safety. Unfortunately, there is always the possibility of Graft vs host disease while transplanting bone marrow.

NK cell therapy is a possible treatment for many different cancers such as Malignant glioma.

Currently Aggressive NK-cell leukemia, being a subtype of PTCL, is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the U.S. Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.

In secondary cases, treatment of the cause, where possible, is indicated. Additionally, treatment for HLH itself is usually required.

While optimal treatment of HLH is still being debated, current treatment regimes usually involve high dose corticosteroids, etoposide and cyclosporin. Intravenous immunoglobulin is also used. Methotrexate and vincristine have also been used. Other medications include cytokine targeted therapy.

An experimental treatment, an anti IFN-gamma monoclonal antibody tentatively named NI-0501, is in clinical trials for treating primary HLH. The FDA awarded breakthrough drug status to NI-0501 in 2016.

While investigational drug therapies exist, no curative drug treatment exists for any of the MPDs. The goal of treatment for ET and PV is prevention of thrombohemorrhagic complications. The goal of treatment for MF is amelioration of anemia, splenomegaly, and other symptoms. Low-dose aspirin is effective in PV and ET. Tyrosine kinase inhibitors like imatinib have improved the prognosis of CML patients to near-normal life expectancy.

Recently, a "JAK2" inhibitor, namely ruxolitinib, has been approved for use in primary myelofibrosis. Trials of these inhibitors are in progress for the treatment of the other myeloproliferative neoplasms.

When primary or secondary resistance invariably develops, salvage therapy is considered. Allogeneic stem cell transplantation can induce durable remissions for heavily pre-treated patients.

Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells.

In 2002, a panel at the International Workshop on Waldenström's Macroglobulinemia agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, weight loss, progressive symptomatic lymphadenopathy or spleen enlargement, and anemia due to bone marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, kidney failure, or symptomatic cryoglobulinemia were also suggested as indications for therapy.

Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. Corticosteroids, such as prednisone, may also be used in combination. Plasmapheresis can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease. Ibrutinib is another agent that has been approved for use in this condition.

Recently, autologous bone marrow transplantation has been added to the available treatment options.

Treatment depends on the grade (I-III) but typically consist of cortisone, rituximab and chemotherapy (etoposide, vincristine, cyclophosphamide, doxorubicin). Methotrexate has been seen to induce LYG. Interferon alpha has been used by the US National Cancer Institute with varying results. In recent years hematopoietic stem cell transplantation has been performed on LYG-patients with relative good success; a 2013 study identifying 10 cases found that 8 patients survived the treatment and were disease free several years later. Two of the disease free patients later died, one from suicide and one from graft versus host disease after a second transplantation 4 years later. The remaining two patients died from sepsis after the transplantation.

ANKL is treated similarly to most B-cell lymphomas. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant.

Most patients will die 2 years after diagnosis.

Currently PTCL is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the US Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.

Pralatrexate is one compound currently under investigations for the treatment of PTCL. For information please consult the US clinical trials database (http://www.clinicaltrials.gov).

Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

There is no consensus regarding the best treatment protocol. Several considerations should be taken into account including age, stage, and prognostic scores (see International Prognostic Index). Patients with advanced disease who are asymptomatic might benefit from a watch and wait approach, as early treatment does not provide survival benefit. When patients are symptomatic, specific treatment is required, which might include various combinations of alkylators, nucleoside analogues, anthracycline-containing chemotherapy regimens (e.g., CHOP), monoclonal antibodies (e.g. rituximab),

radioimmunotherapy, autologous (self) and allogeneic (donor) hematopoietic stem cell transplantation. Follicular lymphoma is regarded as incurable, unless the disease is localized, in which case it can be cured by local irradiation. Although allogeneic stem cell transplantation may be curative, the mortality from the procedure is too high to be a first line option.

In 2010 rituximab was approved by the European Commission for first-line maintenance treatment of follicular lymphoma. Pre-clinical evidence suggests that rituximab could be also used in combination with integrin inhibitors to overcome the resistance to rituximab mediated by stromal cells . However, follicular lymphoma which is CD20 negative will not benefit from Rituximab, which targets CD20.

Trial results released in June 2012 show that bendamustine, a drug first developed in East Germany in the 1960s, more than doubled disease progression-free survival when given along with rituximab. This combination therapy also left patients with fewer side effects than the older treatment (a combination of five drugs—rituximab, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine and prednisone, collectively called R-CHOP).

There are many recent and current clinical trials for follicular lymphoma. For example, personalised idiotype vaccines have shown promise, particularly as upfront therapy, but have still to prove their efficacy in randomized clinical trials.

There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressant therapies. In most reported cases, these cause B cell lymphoproliferative disorders; however, some T cell variations have been described. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus, tacrolimus, or ciclosporin.

Pralatrexate is one compound currently under investigations for the treatment of PTCL.

The prognosis is guarded with an overall mortality of 50%. Poor prognostic factors included HLH associated with malignancy, with half the patients dying by 1.4 months compared to 22.8 months for non-tumour associated HLH patients.

Secondary HLH in some individuals may be self-limited because patients are able to fully recover after having received only supportive medical treatment (i.e., IV immunoglobulin only). However, long-term remission without the use of cytotoxic and immune-suppressive therapies is unlikely in the majority of adults with HLH and in those with involvement of the central nervous system (brain and/or spinal cord).

If treatment has been successful ("complete" or "partial remission"), a person is generally followed up at regular intervals to detect recurrence and monitor for "secondary malignancy" (an uncommon side-effect of some chemotherapy and radiotherapy regimens—the appearance of another form of cancer). In the follow-up, which should be done at pre-determined regular intervals, general anamnesis is combined with complete blood count and determination of lactate dehydrogenase or thymidine kinase in serum.

Treatment can occasionally consist of "watchful waiting" (e.g. in CLL) or symptomatic treatment (e.g. blood transfusions in MDS). The more aggressive forms of disease require treatment with chemotherapy, radiotherapy, immunotherapy and—in some cases—a bone marrow transplant. The use of rituximab has been established for the treatment of B-cell–derived hematologic malignancies, including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).

The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system.

Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised.

In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available.

In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed.

Bone marrow transplant may be possible for Severe Combined Immune Deficiency and other severe immunodeficiences.

Virus-specific T-Lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that has proven to be unsuccessful. It is a treatment that has been effective in preventing and treating viral infections after HSCT. VST therapy uses active donor T-cells that are isolated from alloreactive T-cells which have proven immunity against one or more viruses. Such donor T-cells often cause acute graft-versus-host disease (GVHD), a subject of ongoing investigation. VSTs have been produced primarily by ex-vivo cultures and by the expansion of T-lymphocytes after stimulation with viral antigens. This is carried out by using donor-derived antigen-presenting cells. These new methods have reduced culture time to 10–12 days by using specific cytokines from adult donors or virus-naive cord blood. This treatment is far quicker and with a substantially higher success rate than the 3–6 months it takes to carry out HSCT on a patient diagnosed with a primary immunodeficiency. T-lymphocyte therapies are still in the experimental stage; few are even in clinical trials, none have been FDA approved, and availability in clinical practice may be years or even a decade or more away.

The only known cure for CAEBV is allogenic haematopoietic stem cell transplant (HSCT), with all other treatment options (rituximab, cytotoxic chemotherapy and immunosuppressive therapy) being nothing more than stopgaps.

In a large number of phase I and phase II studies, autologous and allogeneic CIK cells displayed a high cytotoxic potential against a broad range of varying tumor entities, whereas side effects were only minor. In many cases, CIK cell treatment led to complete remissions of tumor burden, prolonged survival durations and improved quality of life, even in advanced disease stages.

Currently, the utilization of CIK cell treatment is restricted to clinical studies, but this therapeutic approach might also benefit patients as first-line treatment modality in the future.

Most patients with "ETV6-ACSL6"-related disease present with findings similar to eosinophilia, hypereosinophila, or chronic eosinophilic leukemia; at least 4 cases presented with eosinophilia plus findings of the red blood cell neoplasm, polycythemia vera; three cases resembled acute myelogenous leukemia; and one case presented with findings of a combined Myelodysplastic syndrome/myeloproliferative neoplasm. Best treatments for "ETV6-ACSL6"-related disease are unclear. Patients with the polycythemia vera form of the disease have been treated by reducing the circulating red blood cell load by phlebotomy or suppressing red blood cell formation using hydroxyurea. Individual case studies report that "ETV6-ACSL6"-associated disease is insensitive to tyrosine kinase inhibitors. Best treatment currently available, therefore, may involve chemotherapy and bone marrow transplantion.